Canine myxomatous mitral valve disease (MMVD) is a common condition in which progressive mitral valve degeneration will often lead to heart failure. Affected dogs typically remain in the preclinical phase for a lengthy period, but once signs of congestive heart failure (CHF) develop, mean survival time is less than 12 months (Häggström et al., 2008). Interventions to delay the onset of CHF are therefore highly clinically valuable. While medical treatment remains the most powerful tool available to prolong the preclinical phase, new evidence suggests that dietary intervention may become a useful complementary approach.
The role of diet in current guidance
Currently, good clinical management of early-stage MMVD consists primarily of defining an appropriate therapeutic regime. The treatment indicated depends on the stage of the disease, with the preclinical phase divided into stage B1 – when there is no significant evidence of cardiac remodelling – and B2 – when left-sided heart enlargement is detected (Atkins et al., 2009). For dogs in stage B2, pimobendan treatment has been shown to significantly delay the onset of CHF (Boswood et al., 2016) and other therapies may also be employed based on individual practitioner judgement. In the 2019 American College of Veterinary Internal Medicine (ACVIM) guidelines, 5 out of 10 panellists recommended using an angiotensin-converting enzyme inhibitor in stage B2 alongside pimobendan (Keene et al., 2019).
In addition to appropriate medical treatment, the ACVIM guidelines for stage B2 recommend paying attention to the diet. A highly palatable diet with enough protein and calories to maintain optimal body condition is suggested, as well as mild sodium restriction to combat sodium retention and fluid overload (Keene et al., 2019). This general dietary guidance is well established; however, recent advances in nutritional science have now opened up the potential for a more specific dietary approach.
Recent advances in metabolomics research
The aim of this more specific dietary approach in MMVD is to tailor nutritional input to support cardiac function and, if possible, maintain the patient in the preclinical phase for as long as possible. Though this rationale is simple, its implementation requires an understanding of the precise metabolic pathways associated with MMVD that can be targeted by nutritional means. It is only recently that these have been elucidated.
Specifically, Purina scientists have conducted a series of “omics” studies to pinpoint key changes in MMVD at the molecular level. These studies indicate that dogs with MMVD have less efficient cardiac energy metabolism than healthy dogs, and this provides a potential target for nutritional intervention (Li et al., 2015).
Nutrition to support cardiac energy metabolism
Over 70 percent of energy in the healthy heart is generated from the mitochondrial oxidation of long-chain fatty acids (Lopaschuk et al., 2010). However, in canine MMVD mitochondrial dysfunction results in compromised fatty acid oxidation (Li et al., 2015). This drives the heart to rely increasingly on the less efficient process of anaerobic glycolysis, resulting in myocardial energy deprivation. To help protect against this, dietary intervention to support fatty acid oxidation could be an effective strategy.
One potential metabolic pathway to influence in such a dietary approach is that concerning carnitine, which is needed to transport long-chain fatty acids into mitochondria for oxidation, helping to produce ATP. Providing carnitine precursors – the amino acids methionine and lysine – helps support fatty acid transport and energy production for the cardiac cells. A further complementary dietary strategy is to reduce the need for this transport by providing an alternative energy source to long-chain fatty acids.
Medium chain triglycerides (MCTs) provide such an alternative. These can cross the mitochondrial membrane without carnitine transport, meaning they are easier to utilise under conditions of cardiac stress. For this reason, medium chain triglycerides have been suggested to complement the management of cardiac disease in humans (Labarthe et al., 2008).
Dietary intervention to reduce oxidative stress
Alongside alterations in energy metabolism, other key metabolic changes identified in MMVD include increased levels of inflammatory mediators and oxidative stress (Li et al., 2015). This suggests another opportunity for dietary intervention, with antioxidants potentially providing a support here. These agents have been recognised for many years for their application in cardiovascular disease, with evidence supporting the use of antioxidants such as vitamin E in cardiac conditions in humans (Pashkow, 2011).
Certain antioxidants are also recognised for other beneficial cardiac effects. For example, omega-3 fatty acids reduce cardiac remodelling and have antiarrhythmic effects (Freeman, 2010), while magnesium can help protect against hypertension (Ozturk et al., 2016). Taurine, a well-known antioxidant, is also needed for normal cardiac function.
New evidence for dietary intervention in canine MMVD
While it is possible to construct a clear rationale for the use of various nutrients in canine MMVD, the complexity of the metabolic changes involved in this condition and the wide range of nutrients implicated underline the need for empirical data to substantiate the effectiveness of any dietary intervention. Such evidence has recently been published, with a blinded, randomised, placebo-controlled study showing a beneficial effect of a diet containing a blend of the nutrients described above on the progression of stage B canine MMVD (Li et al., 2019).
The blend of nutrients in this test diet included taurine, magnesium, the carnitine precursors lysine and methionine, omega-3 fatty acids and vitamin E. Importantly, the diet also utilised medium chain triglycerides as an alternative energy source to support myocardial energy function given the compromised oxidation of long-chain fatty acids in MMVD.
In the study, dogs with MMVD and a similar number of healthy dogs were randomly assigned into two groups. One group was fed the blend of nutrients to support cardiac health (CPB) and the other was fed a control diet (CON).
MMVD dogs fed the blend of nutrients showed an improvement in left atrial size: this effect was evident after three months and persisted throughout the six-month study period. More specifically, a 2.9 percent decrease in left atrial diameter and a decrease in left atrial-to-aortic-root ratio was observed in MMVD CPB-diet dogs after six months. In contrast, MMVD CON-diet dogs showed an increase in both of these measures, with left atrial diameter increasing by 10.8 percent and left atrial-to-aortic-root ratio by 9.5 percent over six months. Mitral regurgitation was reduced in 30 percent of the MMVD CPB-diet dogs during the study (Figure 1). Moreover, while 37 percent of MMVD CON-diet dogs progressed from stage B1 to B2 during the study, none of the MMVD CPB-diet dogs showed progression (Figure 2).
Taken together, the results of this study suggest that dietary management has the potential to delay progression of preclinical canine MMVD. Looking towards the future, dietary modification may prove a valuable element of the management plan for these patients alongside close monitoring and appropriate medical treatment.